Diabetes affects an estimated 374 million people worldwide, including more than 25 million Americans. Diabetic patients are at risk for a wide array of complications, including heart disease, kidney disease (nephropathy), ocular diseases (diabetic retinopathy), and diabetic foot (peripheral neuropathy). Fifteen percent of diabetics wil develop a foot ulcer as a result of peripheral neuropathy during their lifetime. Foot ulcers are th main cause (85%) of lower extremity amputation in patients with diabetes. VisionQuest Biomedical LLC and the University of New Mexico (UNM) have formed a team to study a population of diabetics with and without diagnosed peripheral neuropathy in order to gain a better understanding of how a person's auto-thermo-regulation after a cold provocation reflects neuronal changes in peripheral neuropathy. The study will use standard clinical examinations, such as monofilament sensory tests, as well as less standard exam techniques, such as sympathetic skin response, to compare with dynamic infrared functional imaging. The functional infrared imaging techniques have been developed and applied by our group as part of a pilot study. A prototype functional thermal imaging device has been tested on a number of subjects that shows strong indications of its capacity to measure thermal regulation in the plantar foot, and demonstrates potential as a biomarker for accurate quantification of DPN changes/progression in type 1 (T1D) or type 2 diabetes (T2D). Our preliminary experimental data results produced highly compelling evidence that thermal-functional technology can detect differences between normal controls and diabetics with/or at risk for peripheral neuropathy. There are three specific aims to be accomplished in this grant application. The first aim is to establish a normative range for the functional response to thermal stimulus as measured by an infrared imaging device by studying 50 control subjects. In the second aim, we will study the variation in the thermally derived functional signal in 50 diabetics with diagnosed peripheral neuropathy. The third aim is to apply the protocol developed in Aim 1 to conduct a clinical study with 50 diagnosed subjects with diabetes without peripheral neuropathy. Features, such as recovery time, recovery pattern (both temporal and spatial), will be correlated with clinical diagnostic measurements, such as nerve conduction velocity tests and ankle-brachial index tests. Clinical examinations will be performed by our collaborating podiatrist.